Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna

Research output: Contribution to journalArticle

Authors

  • Philipp Antczak
  • Anirudha Giri
  • Mark T D Cronin
  • Chris Vulpe
  • Francesco Falciani

Colleges, School and Institutes

External organisations

  • UC Berkeley
  • University of Liverpool
  • Liverpool John Moores University
  • Centre for Computational Biology and Modelling
  • Institute for Integrative Biology
  • Assam University
  • Nutritional Sciences and Toxicology and Berkeley Institute of the Environment, University of California

Abstract

The expanding diversity and ever increasing amounts of man-made chemicals discharged to the environment pose largely unknown hazards to ecosystem and human health. The concept of adverse outcome pathways (AOPs) emerged as a comprehensive framework for risk assessment. However, the limited mechanistic information available for most chemicals and a lack of biological pathway annotation in many species represent significant challenges to effective implementation of this approach. Here, a systems level, multistep modeling strategy demonstrates how to integrate information on chemical structure with mechanistic insight from genomic studies, and phenotypic effects to define a putative adverse outcome pathway. Results indicated that transcriptional changes indicative of intracellular calcium mobilization were significantly overrepresented in Daphnia magna (DM) exposed to sublethal doses of presumed narcotic chemicals with log K<inf>ow</inf> ≥ 1.8. Treatment of DM with a calcium ATPase pump inhibitor substantially recapitulated the common transcriptional changes. We hypothesize that calcium mobilization is a potential key molecular initiating event in DM basal (narcosis) toxicity. Heart beat rate analysis and metabolome analysis indicated sublethal effects consistent with perturbations of calcium preceding overt acute toxicity. Together, the results indicate that altered calcium homeostasis may be a key early event in basal toxicity or narcosis induced by lipophilic compounds.

Details

Original languageEnglish
Pages (from-to)11132-11140
Number of pages9
JournalEnvironmental Science & Technology
Volume49
Issue number18
Publication statusPublished - 15 Sep 2015

ASJC Scopus subject areas